Sickle Cell DIsease, G6PD Deficiency & Other Hemolytic Anemias Flashcards
Disease that gives inherent resistance to Falciparum malariae
Sickle Cell Disease
What causes the formation of HbS in SCD?
Replacement of Glutamate with Valine at Beta-6 position
What makes the RBC sticky in SCD? What are it’s consequences?
HbS polymerization makes the RBC sticky and it results in micro-occlusions in blood vessels, leading to organ infarction.
Do the px. w/ SCD present with pathological jaundice? Why?
Nope. Cuz for the 1st 6 months after birth, HbF plays a protective role and the damaged HbS doesn’t show symptoms.
Till what age is SCD asymptomatic?
Till 6 months of age. Beyond which HbF decreases and the patient starts showing symptoms of SCD.
Most common presentation of SCD? Other symptoms?
Most common: Fever>Pain (d/t vaso-occlusive crisis)
Age of presentation of Hand Foot Syndrome?
HFS presents in >5yrs old children.
Hand foot syndrome vs Osteomyelitis
HFS can be confused with osteomyelitis but the difference is that OM mostly has infective etiology and mostly affects the long bones, U.L HFS.
Hand foot syndrome also seen in?
A.S.I px. undergoing chemotherapy with Capecitabane or 5-Fluorouracil. Known as Palmer-Planter Acrodysthesia.
Symptoms include: Redness, desquamation & pain over palm and sole of foot
DOC for pulmonary artery HTN
Bosentan
Autosplenectomy predisposes px. to what organisms? Mgmt.?
Capsulated organisms (Pneumococcus, Meningiococcus, H. inlfuenza)
Managed by vaccination
Acute chest syndrome vs Acute coronary syndrome
- Acute chest syndrome occurs due to occlusion of small coronary vessels by the sticky HbS, leading to coronary infarction.
- Acute coronary syndrome is due to atherosclerosis.
Homozygous vs heterozygous SCD
HOMOZYGOUS
- early & more severe manifestation (~3yrs of age) - A.K.A Sickle cell DISEASE - Lack HbA (HbS, HbF, HbA2 present)
HETEROZYGOUS
- late presentation cuz px. already has enough HbA to avoid symptoms but will develop symptoms oof SCD with some triggers like dehydration & hypoxia which causes HbS polymerization leading to sickling episodes. - A.K.A Sickle cell TRAIT - Has all 4 types of Hb (HbS, HbF, HbA & HbA2) present
IOC for SCD
High Performance Liquid Chromatography > Hb Electrophoresis
Workup of a SCD px.
1) Peripheral smear: i) Dec. Hb d/t extravascular hemolysis
d/t rigid RBCs stuck in splenic
capillaries —— J.L Hered. Sphero.)
ii) Sickle cell
2) Reticulocyte count: Increased (J.L other hemolytic anemias)
3) IOC: HPLC>Hb electrophoresis (High Performance Liq. Chromatog.)
4) USG abdomen: to evaluate spleen size and kidney status
5) Echo T.T.E: to evaluate ischemic/dilated cardiomyopathy
6) X-Ray Hand/Foot: to look for dactylitis and to R/O osteomyelitis
Management of SCD
1) Hydroxyurea (decreases sickling episodes)
2) Fentanyl/Morphine/Codeine (for bone pain)
3) Bosentan if PAH present
4) During sickling episodes: i) Analgesics mentioned in (2)
ii) Whole blood transfusion
- Packed RBCs not given as it will increase the viscosity of blood leading to increased incidence of sickling episodes.
- No TOC for SCD
Peripheral smear findings in splenectomy patients
1) Cabot Ring
2) Howell Jolly Bodies
Symptoms of SCD
1) Fever and pain
2) Hand Foot Syndrome (Dactylitis) caused by occlusion of nutrient artery by HbS.
3) Avascular necrosis of bone (MRI)
4) Autosplenectomy (~3yr) d/t splenic infarction
5) Coronary infarction leading to dilated cardiomyopathy (— causing acute chest syndrome)
6) Pulmonary vaso-occlusive episodes (PAH)
7) Kidney - Papillary necrosis/isostheuria (inability to conc. & dilute urine d/t damage to the collecting duct present at the renal papilla)
8) Hemolytic gall stones
9) Non-healing ulcers on medial malleolus (J.L: Hered. Sphero.)
10) Aplastic Crisis (Human Parvo virus B19)
Triggers of G6PD def.
1) Fava beans
2) Antimalarial drugs (Primaquine)
3) Aspirin
4) Nitrofurantoin etc.
Function of G6PD? What happens in G6PDD?
Neutralizes the free radical induced damage inside RBC
In G6PDD, unopposed oxidative stress leads to complement mediated intravascular hemolysis, resulting in hemoglobinemia (Free Hb in blood) which in turn leads to hemoglobinuria (black urine). Hemoglobinuria may lead to acute tubular necrosis [d/t blockage of tubules by hemoglobin (high molecular wt.)], causing death.
M.C.C of death in px. w/ G6PDD
Acute tubular necrosis
Kind of hemolysis in G6PDD
G6PDD is an example of INTRAVASCULAR as well as EXTRAVASCULAR hemolysis.
- If the question mentions a trigger (like fava beans intake or administration of anti-malarial drugs), then it’s INTRAvascular hemolysis.
Drugs to be avoided in G6PDD
“PCM NA”
P: Primaquine
C: Chloroquine
M: Mefloquine
N: Nitrofurantoin
A: Aspirin, sulfa drugs (Sulfonamide)
Anti-malarial drugs that can be given to G6PDD px.
1) Artesunate
2) Artemisinin
Two major classes of antibodies causing Auto-Immune Hemolytic anemias
1) Warm antibodies (IgG class)
2) Cold Antibodies (IgG & IgM)
Examples of warm antibodies
1) SLE
2) CLL (m.c adult blood cancer)
3) . NHL
4) Alpha-Methldopa
Types and features of Cold Antibodies mediated AIHA
Two types: 1) Paroxysmal Cold Hemoglobinuria (IgG mediated)
- Mycoplasma pneumoniae inf. leads to production of DONATH LANDSTEINER ANTIBODIES which attacks self RBCs at low body temp. leading to hemoglobinemia and then to hemoglobinuria.
2) Cold-agglutinin syndrome (IgM mediated)
- Molting of the acral parts (tip of nose, earlobes, fingertips)
- BLACK URINE
How does Donath Landsteiner Ab cause AIHA?
DONATH LANDSTEINER ANTIBODIES, which normally attacks the bacteria (Mycoplasma pneumoniae) may end up accidentally attacking self RBCs. This happens because DLA usually attacks the “M Protein” on the surface of the bacteria and RBCs also have a protein structurally similar to the M proteins on the bacteria.
Presentation of px. w/ AIHA
- Pallor, body malaise/chest pain
- Palpitations/Pedal edema
Work up of AIHA
- Peripheral smear: i) Dec. Hb
ii) Spherocytes (A.S.I Hered. Sphero.) - IOC: Direct Coomb’s Test
Management of AIHA
Cause specific but usually steroids
Peripheral smear characteristics of Microangiopathic Hemolytic Anemia
- Schistocytes/HELMET CELLS
- Echinoctes/BURR CELLS
- MAHA: Complement mediated damage to RBC
Causes of MAHA
1) Hemolytic Uremic Syndrome (caused by E.coli 0157 H7 which is an enterohemorrhagic E. coli and releases shiga toxin causes activation of complement system and in turn MAHA)
2) Thrombotic Thrombocytopenic Purpura (Variant of HUS)
PENTAD - i) Fever
ii) Acute Ischemic Stroke
iii) Hemolysis
iv) Uremia/Renal variety AKI
v) Purpura (Palpable bleed)
3) Metallic Prosthetic Heart Valves
Work up of px. w/ MAHA
1) Direct Coombs Test: NEGATIVE (HA are always positive for coombs test. So, MAHA is a.k.a Cooombs negative hemolytic anemia)
2) Peripheral smear: Helmet cells and Burr cells
Management of MAHA
Cause specific (Usually conservative. If HUS: Dialysis)
Investigations/work up in G6PDD px.
1) G6PD Assay (IOC)
2) Peripheral smear: i) Dec. Hb
ii) BITE CELLS
iii) HEINZ BODIES [on Supravital (Crystal violet) stain]
- Heinz bodies: Denatured Hb d/t oxidative stress
IOC for G6PDD
G6PD assay
Blood smear results:
1) Flower cells
2) Sezary cells
3) Mott cells
4) Spurr cell/Acanthocytes
5) Schistocyte/Helmet cells
6) Howel Jolly Bodies and Calot rings
1) Flower cells: Adult T cell leukemia by HTLV-1
2) Sezary Cells: T cell Non-Hodgkin’s Lmphoma
3) Mott cells: Multiple Myeloma (Russel bodies)
4) Spurr cell/Acanthocytes: Abetalipoproteinemia (caused by Vit. E def.)
5) Schistocytes/Helmet cells: HUS/TTP
6) Howel jolly bodies and Calot rings: Asplenia
